tbuckley/cabot-search huggingface dataset:
Increasing COVID-19 vaccine adherence within an immunocompromised patient population in a community practice.
Authors: Jane Charlotte Tolkinen, Carolyn Anne Carrera, Sunaina Gowda Ramesh Babu, Barry DeCicco
Journal: Journal of Clinical Oncology (2023)

e18714 Background: Patients receiving antineoplastic therapy are at increased risk of severe illness and death from COVID-19. Vaccination against COVID-19 is an effective strategy to prevent serious complications of the disease. Because immunocompromised patients may have a blunted immune response to COVID-19 vaccinations, the CDC recommends these patients receive an additional vaccine dose. CDC recommendations serve as a guideline for optimal care of hematology/oncology patients, and within which we demonstrate a quality improvement project to promote community education and assess vaccination rates. Methods: Through Epic electronic medical record (EMR) reporting, we identified 250 immunocompromised patients who had not completed their primary COVID-19 vaccination series or booster and initiated antineoplastic therapy between 12/1/2020- 12/1/2021 at a community-based oncology practice in Michigan. Patients were provided an electronic patient portal letter detailing vaccination recommendations, information on how to obtain vaccination, and a survey inquiring if patients were more likely to become vaccinated after the educational intervention. 204 patients received electronic letters and 46 patients (without portal access) were sent a letter via the US postal service. Three months post intervention, we evaluated for change in COVID vaccination status, hospitalization, death rates, and patient preferences regarding vaccination. Results: Three months post intervention, a total of 44 patients responded to the survey (39 electronically and 5 via mail). The overall improvement in vaccination rate was 10.4%. Using Fisher’s exact test, we found a statistically significant difference (p = 0.002) in vaccination rates between survey responders compared to non-responders. Vaccination rates increased by 25.0% in survey responders, compared to 7.3% in patients who did not respond. During the study period, 13 patients contracted COVID-19 (1/13 vaccinated), and one patient required hospitalization due to COVID-19 (unvaccinated). No deaths due to COVID-19 were reported. Patients’ most cited reasons for declining vaccination were concerns regarding vaccination safety and lack of understanding of the CDC recommendations. Conclusions: Our study highlights the EMR as an effective means to provide community education about COVID-19 vaccination. Limitations include delayed outreach to patients without electronic patient portal access or with infrequent patient portal use. Nonetheless, our quality study design serves as a model for other implementations of electronic community outreach in oncology patients. Future directions will assess long-term vaccination rates and outcomes in these immunocompromised patients.
Expanding the spectrum of neoplasms harboring <i>EWSR1:CREM </i>fusion as detected by a real-world clinical genomics platform.
Authors: Leticia Campoverde, Mark Gordon Evans, Andrew Elliott, Felipe Camacho, Jeremy Adler, Matthew James Oberley, George W. Sledge, Andrew E. Rosenberg, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2023)

e15061 Background: Malignancies with various well-defined phenotypes and prognoses have been shown to possess gene fusions between Ewing Sarcoma Breakpoint Region 1 ( EWSR1) and one of the CREB family genes, specifically CREB1 and ATF1. However, less is known about neoplasms that harbor EWSR1:CREM rearrangements, which are thought to result in constitutive activation of CREM and subsequent dysregulation of oncogenes, such as BCL-2 family genes, EGFR1, and cyclins. EWSR1:CREM fusion has been identified in rare cases of angiomatoid fibrous histiocytoma, clear cell sarcoma, hyalinizing clear cell carcinoma of the head and neck, and intracranial myxoid mesenchymal tumor. Our study represents the largest to date and seeks to expand and further define the diversity of tumor subtypes that possess EWSR1:CREM fusions. Methods: Detection of EWSR1:CREM rearrangements by whole transcriptome sequencing was performed for &gt; 240,000 neoplasms submitted to Caris Life Sciences (Phoenix, AZ). Histological review of the identified tumors was performed by two board-certified pathologists (MGE, AER). Treatment and outcome information were collected, where available. Results: An EWSR1:CREM fusion was detected in 18 cases, which included one intracranial myxoid mesenchymal tumor, one mesothelioma, four hyalinizing clear cell carcinomas of the head and neck, two clear cell sarcomas, two small round and spindle cell sarcomas, and eight histologically malignant tumors having an epithelioid morphology. While the latter were in keeping with a disease entity recently reported in the medical literature (epithelioid neoplasm with predilection for mesothelial-lined cavities), several of these cases demonstrated unexpected neuroendocrine differentiation and were found at unusual sites, including the kidney, uterus, and cervical spine. Moreover, three cases had the features of squamous cell carcinoma. Surgical resection was performed in all patients, and pazopanib was utilized in two round and spindle cell sarcoma cases. This medication was shown radiographically to produce a partial response at 19 months and stable disease at 26 months, respectively, in heavily pretreated patients. Conclusions: By detecting an EWSR1:CREM rearrangement, molecular testing may aid in the diagnosis of a variety of rare tumor types, including a poorly understood malignant epithelioid neoplasm that arises in a variety of anatomic sites including mesothelial-lined cavities. Tumors harboring this fusion may ultimately be susceptible to treatment with tyrosine kinase inhibitor targeted therapy.
Comprehensive 0utcomes for After Cancer Health: COACH.
Authors: Robin Mary Lally, Rachael Schmidt, Gisele Tlusty, Mariah Kay Jackson, Elizabeth Arthur, Austin Barr, Laura Flora, Marilyn J. Hammer, Jessica Trevino Jones, Debra Lynch Kelly, Jessica L. Krok-Schoen, Jennifer Loftis, Leorey Saligan, Angela Starkweather, Michael Vazquez, Meagan Whisenant, Alexi A. Wright, Kelly Jean Brassil
Journal: Journal of Clinical Oncology (2023)

TPS12141 Background: The landscape for cancer survivors continues to evolve as individuals live longer following primary therapy. For some, treatment is complete; for others, active surveillance or maintenance therapy may be indicated. Individual survivorship needs are diverse, influenced by tumor and treatment type, as well as social determinants of health. Digital interventions may support survivors in achieving personalized health goals throughout survivorship. The Comprehensive Outcomes for After Cancer Health (COACH) Study (NCT05349227) explores the feasibility of a digital health coaching (DHC) program for individuals enrolled with diverse tumor types and geographic regions. Methods: COACH is a multi-center, randomized, wait-list control trial enrolling 550 individuals ≥18 years old who are within 1-year of completion of primary cancer therapy at enrollment. Up to 100 participants, will be recruited at each of 6 study sites, of which 3 are currently enrolling. Consented individuals are randomized to 6 months of DHC or 6 months of data collection only, then cross-over for follow-up to 12-months. Both groups wear an activity tracker; complete patient reported outcome measures; and provide fecal specimens. The DHC program includes weekly Health Advisor calls and supplemental delivery of evidenced-based content via text, email or mobile platform. Topics fall in health domains of physical, mental/emotional, financial, social, and sexual, and emphasize nutrition, physical activity, sleep, and screening for recurrent or de novo cancer. Feasibility for this study is defined as a retention rate greater than or equal to 70%, and acceptability will be defined as less than or equal to 20% scoring “not at all helpful.” Trends over time will be assessed using linear mixed models using time as a fixed effect, as well as any covariates and interactions of interest. Descriptive statistics will be used to evaluate exploratory endpoints. A cross-cohort end-point related to physical function as measured by the PROMIS Physical Function 10a, will also be evaluated. To date, 72 individuals have enrolled, with Nebraska as the lead site, including 71 women, with a mean age of 61.78 (Range 33-74), from the U.S. Midwest (n = 57) and Northeast (n = 15). 4 identify as African American/Black, 68 as White. 50 have a breast, 13 ovarian, 8 endometrial, 1 gastric diagnosis. Nine have completed the first 6 months of the study. The study is novel in the breadth of data collected and potential to understand variability in patient experiences and provide insights into the feasibility, acceptability, and efficacy of a DHC intervention supporting individuals after primary cancer treatment. Clinical trial information: NCT05349227 .
Clinical outcomes by <i>SF3B1</i> mutation status in patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) retreated with erythropoiesis-stimulating agents (ESAs).
Authors: Adeola Y. Makinde, Guillermo Garcia-Manero, Rayna K. Matsuno, Ali McBride, Thomas D. Brown, Danny Idryo, Ronda Broome, Autumn Herriman, Kristiana Wilkinson, Sheetal Walters, Andrew Schrag, Hina Mohammed, Monika A. Izano, Sudipto Mukherjee
Journal: Journal of Clinical Oncology (2023)

7071 Background: Pts with SF3B1-mutated LR-MDS often have a more favorable prognosis versus those with SF3B1 wildtype. A sizeable number of pts with LR-MDS undergo ESA treatment even after experiencing ESA failure in first line. This study evaluated the outcomes of pts with LR-MDS retreated with ESAs in routine clinical practice, stratified by SF3B1 status. Methods: This retrospective cohort study included pts with LR-MDS in the US community setting who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019, and were followed through June 30, 2021. Eligible pts discontinued ESAs (treatment gap ≥ 3 wk for epoetin alfa or ≥ 6 wk for darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Ring sideroblasts (RS) ≥ 15% served as a surrogate for pts with unknown SF3B1 mutation status. Outcomes included ESA switches, dose reductions and escalations, ESA failure, and overall survival (OS). Primary ESA failure was defined as no rise in hemoglobin (Hb) ≥ 1.5 g/dL or no decrease in RBC transfusion requirement by 8 wk of treatment. Transfusion-dependent (TD) status was evaluated for pts who were transfusion independent (TI) at baseline. Results: A total of 82 pts with LR-MDS and repeat ESA treatment were included. Median age at start of ESA treatment was 79 y (interquartile range [IQR], 72–85). Diagnosis of MDS-RS, MDS with isolated del(5q), MDS with multilineage dysplasia, and MDS with single lineage dysplasia was reported in 30 (36%), 7 (9%), 9 (11%), and 9 (11%) pts, respectively; 27 (33%) had unknown classification. Median follow-up was 26 mo (IQR, 13–38) with 65% failing ESA therapy by 8 wk. Table shows pts’ SF3B1 mutation status, median OS, pts who had an ESA switch, dose reduction or escalation, experienced ESA failure, and pts who were TI at baseline and became TD during follow-up. Results were similar when RS was not used as a surrogate, and when analyses were limited to pts who were treated with ESAs only throughout follow-up. Conclusions: In this study of pts with LR-MDS retreated with ESAs, primary ESA failure was high with nearly half of TI pts becoming TD during follow-up. OS was poor regardless of SF3B1 status – 2–4 times lower than the remaining life expectancy for a 79-y-old (108 mo for men; 125 mo for women). Although treatment options were limited during the study period, the high primary failure rate suggests that pts with LR-MDS may benefit from alternatives to ESAs. [Table: see text]
Comparison of efficacy between immune checkpoint inhibitors and irinotecan-based chemotherapy as third-line treatment for patients with advanced gastric cancer: A Korean real-world multicenter study (KCSG ST22-06).
Authors: Sung Hee Lim, Jae-Joon Kim, Hyeon-Su Im, Hye Sook Han, In-Ho Kim, Dong-Hoe Koo, Jang Ho Cho, Chi Hoon Maeng, Min-Young Lee, Hyo Jin Lee, Jwa Hoon Kim, Sang Gon Park, Joo Young Jung, Seong Hoon Shin, Ki Hyang Kim, Keun-Wook Lee, Sun Young Rha
Journal: Journal of Clinical Oncology (2023)

e16047 Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy are frequently used after paclitaxel plus ramucirumab as second-line treatment for patients with recurrent and/or metastatic gastric cancer (RMGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with RMGC. Methods: We retrospectively reviewed patients with RMGC, whose third-line treatment started between July 2019 and June 2021 at 17 centers in South Korea. The ICI group included patients who received nivolumab or pembrolizumab and the irinotecan-based chemotherapy group included those patients who received irinotecan or FOLFIRI. Results: A total of 363 patients (129 in the ICI group and 234 in the irinotecan-based chemotherapy group) were analyzed. The median progression-free survival (PFS) was 2.2 and 2.9 months in the ICI and irinotecan-based chemotherapy groups, respectively. The median overall survival (OS) was 5.5 months (95% CI, 3.6-7.4) in the ICI group and 6.0 months (95% CI, 4.8-7.0) in the irinotecan-based chemotherapy group [HR 0.97 (95% CI, 0.75-1.25); P=0.786]. Multivariable Cox-regression analysis showed that weight loss, peritoneal metastasis, low serum sodium, low serum albumin and short duration of second-line treatment were associated with inferior OS ( P&lt;0.05), meanwhile microsatellite instability-high (MSI-H)/mismatch repair-deficient (MMR-D) tumor was an independent prognostic factor for superior OS. The ICI group showed significantly longer OS than the irinotecan-based chemotherapy group in patients without peritoneal metastasis [HR 0.54 (95% CI 0.30-0.99); P=0.047)]. Whereas the irinotecan-based chemotherapy group showed significantly longer OS in patients without PD-L1 expression [HR 1.62 (95% CI 1.03-2.55); P=0.037] than the ICI group. Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for patients with RMGC. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.
Neoadjuvant tislelizumab combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Single arm phase II study.
Authors: Peng Jin, Yong sheng Gao, Zheng Fu, Wen feng Yang, Xue Meng
Journal: Journal of Clinical Oncology (2023)

4068 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. Methods: This is a prospective single-arm clinical trial. A total of 20 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy (radiotherapy: 41.4Gy in 23 fractions; chemotherapy: Paclitaxel (Albumin bound) 100mg/m 2 , and Cisplatin 75 mg/m 2 once every 3 weeks for 2 cycles.) Radical esophagectomy was performed within 4-6 weeks after neoadjuvant therapy. PET/CT was performed at baseline and before surgery. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immune biomarker to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. Results: Twenty patients enrolled, all of whom received neoadjuvant tislelizumab combined with chemoradiotherapy. Eighteen patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 18 patients who underwent surgery, R0 was 100% (18/18), 9 patients achieved pCR (50.0%), and 13 patients achieved MPR (72.2%). Most of treatment-related adverse event (TRAE) were grade 1-2, and the most common TRAE was anemia (15, 75.0%). The grade 3 TRAE included 1 leukopenia (5.0%), 1 neutropenia (5.0%), 1 liver damage (5.0%), and 1 elevated cardiac troponin T (5.0%). A significant decrease in SUVmax was observed in both pCR and no-pCR patients after treatment. Baseline SUVmax in no-pCR patients tended to be higher than pCR patients(p=0.0642). Furthermore, a significant increase in circulating CD4 + T cells, CD4 + effector memory T cells (T EM ), and M1 were found after treatment. Among the patients with pCR, the CD4 + T EM and cDCs after treatment were higher than those in the no-pCR patients, while Tregs and M2 were lower. Conclusions: Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety. Clinical trial information: NCT05323890 . [Table: see text]
Clonal hematopoiesis (CH) associated mutations in patients with advanced solid tumors enrolled in phase I clinical trials.
Authors: Julieta Rodriguez, Arnaud Bayle, Arnaud Pages, Francois-Xavier Danlos, Damien Vasseur, Etienne Rouleau, Ludovic Lacroix, Beatriz Alonso de Castro, Vincent Goldschmidt, Lauren Seknazi, Antoine Hollebecque, Jean-Marie Michot, Stephane Champiat, Aurelien Marabelle, Kaissa Ouali, Christophe Marzac, Santiago Ponce Aix, Antoine Italiano, Jean Baptiste Micol, Capucine Baldini
Journal: Journal of Clinical Oncology (2023)

3056 Background: An increased number of CH associated mutations has been identified in patients (pts) with solid tumors. Their impact on pts outcomes remains unclear. This study aims to integrate molecular data and clinical characteristics of CH in pts enrolled phase I clinical trials. Methods: Data was collected retrospectively from medical records and molecular profile reports (Foundation One Liquid CDx Assay – 309 genes) performed before first study drug administration at the Drug Development department in Gustave Roussy (Villejuif, France) within the STING trial (NCT04932525). CH prevalence was assessed according to a variant allele frequency (VAF) threshold of 1% in epigenetic modifiers ( DNMT3A, TET2 and ASXL1). Results: From January 2021 to December 2022, 255 pts were enrolled in a phase I clinical trial and had a liquid biopsy. In total, 55% of patients were male with a median age of 62 years [24-86]. Most common tumor locations were gastrointestinal (27%), genitourinary (21%) and thorax (18%). Patients received a median of 2 prior lines of treatment before investigational study drug and CH assessment. At the end of the data cut off, 81% of pts discontinued phase I treatment mostly due to progression disease. Overall, 104 pts (41%) had at least 1 CH mutation in liquid biopsy at baseline with 55 pts (22%) at a VAF of ³ 1%. Mutation frequency was DNMT3A in 42% (n= 23), ASXL1 in 38% (n=21) and TET2 in 31% (n=17). Co-mutations were present in 26 patients, with the most frequent being DNMT3A + ASXL1. Median PFS and OS were 3.7 months (m) for CH group vs 3.5m for no-CH (p=0.3) and 24m CH vs 15m no-CH (p=0.5), respectively. Conclusions: CH is commonly found in pts with solid tumors treated in phase I trials, with a prevalence in our cohort of 22%. Most frequent mutated gene was DNMT3A. Prognostic implications of the impact of these mutations in patient´s outcomes remain to be elucidated and will be presented at the meeting.
Results of a retrospective multicenter study comparing the effectiveness of regorafenib and the rechallenge of chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Evgenia Kuzmina, Mikhail Fedyanin, Igor Reshetov, Sergey Parts, Ilya Pokataev, Maxim Polyanskiy, Tatiana Antonova, Dmirii Pikulin, Evgenia Arseneva, Marina Anikina, Pavel Golubev, Anna Syskova, Vsevolod Galkin
Journal: Journal of Clinical Oncology (2023)

e15561 Background: Regorafenib is considered the standard third-line therapy of mCRC. However, the modest efficacy and significant toxicity of regorafenib urges the search for new therapeutic approaches. In various countries, the re-challenge of the previously effective treatment regimens is being considered. We compared the effectiveness of various variants of systemic therapy in the third and subsequent lines of the treatment. Methods: We analyzed the prospective database of pts with mCRC from two clinics of the Russian Federation. The statistical hypothesis implied the equivalence of the 6-month overall survival on the repeated chemotherapy (CT) and targeted therapy with the third line regorafenib therapy, provided the equivalence boundaries from 0.8 to 1.25. With α = 0.05, the study power is 80% with 178 patients, 89 people in each group. We conducted statistical analysis with the SPSS statistical software package (v. 20, IBM). Results: In the database, we identified 215 patients with morphologically confirmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. Of them, we selected 132 patients with a history of regorafenib therapy, and 83 patients with the re-challenge of CT as the third line of the therapy. Overall survival (OS) in the re-challenge and regorafenib groups did not differ (hazard ratio [HR] 1.01 with 95%CI 0.7-1.45; p = 0.9) and the 6-month OS was 74 and 70%, respectively. Progression-free survival was significantly higher in the re-challenge group (HR 1.94 with 95%CI 1.3-2.7; p &lt; 0.001); In the multifactorial analysis, the re-challenge of previous treatment regimens kept its independent positive effect on progression-free survival (HR 1.9 with 95%CI 1.3-2.8; p = 0.0001) also as index T &lt; 3 (HR 0.7, 95CI 0.55-0,94); ECOG ≥1 a (HR 1.5 with 95%CI 1.16-2.05; p &lt; 0.01) affected PFS negatively. The reduction of the regorafenib dose did not affect PFS (HR 0.9 with 95% CI from 0.9 to 1.0; p = 0.1), its starting dose (HR 0.9 with 95 CI from 0.9 to 1.0; p = 0.2), and a break in the regorafenib treatment (HR 0.9 with 95% CI from 0.5 to 1.8; p = 0.9). Conclusions: Regorafenib and the re-challenge of previously effective CT in the third-line of mCRP therapy show the similar 6-mon. OS. However, progression-free survival is significantly higher in the re-challenge group in third line therapy.